Effect of pentobarbital on the disposition of alprenolol

Alprenolol was administered orally and intravenously to 5 healthy subjects before and after 10 to 14 daily doses of 0.1 gm pentobarbital. The area under the plasma concentration time curve after an oral 200-mg dose decreased from 706 +/- 277 to 154 +/- 48 ng/ml-hr (mean and SD) with the barbiturate treatment, but there was no significant change in elimination rate. The change in area corresponded to an increase in extraction by the liver from 0.72 +/- 0.13 to 0.93 +/- 0.01. The disposition of a 5.0-mg intravenous dose of alprenolol did not change significantly after pentobarbital treatment. There was no indication of a marked change in hepatic blood flow estimated from the clearance of alprenolol after intravenous administration. It is concluded that pentobarbital administration induces the metabolism of alprenolol in man and that the pharmacokinetic theories derived for hepatic extraction of drugs subject to a high metabolic clearance can be successfully applied.